The proposed research will use EM autoradiography to determine the numbers an distributions of acetylcholinesterase (AChE) and acetylcholinereceptors (AChR) at the vertebrate neuromuscular junction (nmj). The numbers obtained, will be used to build a model (the saturated disk model) of neuromuscular function, which make specific physiological predictions. Voltage clamp studies on the time course of endplate currents (mepcs and epcs) will be correlated with the normal and experimentally varied receptor and esterase site densities. These studies will allow us to determine how the molecular organization of AChE and AChR underlies the physiology of the nmj. We hope thereby to derive the kinetic contstants that control endplate currents. We will also study the neurothrophic control of the development and turnover of AChR and AChE in normal and diseased muscle. The possible role of Ca ions in mediating muscle necrosis after esterase inactivation will be examined.